As used herein, the term "stabilized composition" refers to an aqueous solution for therapeutic use, containing at least one small or medium-size biologically active peptide. Such stabilization should allow the composition to be stored at room temperature for extended periods without loss in biological activity.
A substantial number of biologically active peptides, their derivatives and analogs (in the following termed "peptides") are known to be therapeutically useful. For various reasons they are often administered in form of aqueous compositons, that is, sterile aqueous solutions containing a known amount of peptide.
The biological activity of the peptides to be administered is often extremely high. Thus, only very small amounts of peptide are needed for a single does. Such dilute aqueous peptide solutions in general are not stable at room temperature for longer periods, even if kept in sealed containers. The therapeutically active peptide hormone analog desmospressin is such a peptide. Its aqueous solution has to be stored at a temperature not exceeding 8.degree. C. Storage at higher temperaturs such as, for instance, room temperature, results in the degradation of desmopressin by hydrolytic and/or oxidative processes which are not blocked by the addition of a preservative, such as chlorobutanol (1,1,1-trichloro-2-methylpropan-2-ol). However, chlorobutanol effectively protects desmopressin against microbial attack.
Another problem with dilute aqueous solutions of peptides is the adsorption of minute amounts of peptide to the walls of the container in which the solution is kept. Since such peptide solutions are usually very dilute, adsorption of even minor amounts may substantially reduce the amount of peptide available for administration.
A particularly attractive way of administration of small and medium-size peptides in solution is via the nasal mucosa, either as drops or in spray form, which is even more convenient and more reproducible. Desmopressin, for instance, can be administered in an aqueous, 0.9 % sodium chloride solution (saline) by this route.
Various kinds of intranasal spray delivery devices are known in the art. In general, peptides in an aqueous solution are administered by means of metered-dose spray pumps, such as those manufactured by Ing. Erich Pfeiffer KG, Radolfzell, Germany. An alternate route is via a graduated plastic tube of special design called a "rhinyle" which is partially filled with an aqueous solution containing a peptide. One end of the rhinyle is placed in the mouth and the other end is placed in the desired nostril, The solution is then delivered to the nostril by blowing.
Peptides for nasal administration often have extremely high biological activity, and only a very small amount of peptide is needed in a single dose. However, the particular form of administration may require a minimum liquid volume for good reproducibility. Thus, effective concentration ranges for nasally administered peptides are generally quite low. For instance, a single desmopressin dose for nasal administration is typically between 10 .mu.g to 40 .mu.g, but may even be as little as 2.5 .mu.g and as high as 300 .mu.g. Typical dose volumes are from 100 .mu.l to 400 .mu.l (4.times.100 .mu.l). These doses are normally taken on a regular basis, such as at least once daily.